SUMMARY
Beta-catenin signaling is required for hair follicle development and regeneration which are involved in the resuscitation of hair follicle stem cells (HFSCs). To further characterize the role of beta-catenin in the regulation of proliferation of HFSCs, the beta-catenin expression was measured in the defined stages of hair follicle cycle and the proliferative potency was determined by using an in vitro cell growth assay. Our results showed that activation of beta-catenin correlated with HFSCs proliferation, which appeared to be mediated by the nuclear translocation of stabilized beta-catenin and the activation of responsible cell cycle genes (cyclin D1 and p21). In addition, PI3K/Akt pathway was also involved in the HFSCs proliferation, partly regulated by beta-catenin signaling pathway. These results demonstrate that beta-catenin is an essential factor in the regulation of HFSCs proliferation via PI3K/Akt pathway and might be a potential therapeutic target for the regulation of the yield of keratinocytes from HFSCs.
KEY WORDS
beta-catenin; hair follicle stem cell; proliferation; PI3K/Akt; cyclin D1; p21
REFERENCES
Blanpain C. Impact of beta-catenin signaling pathway on stem cell differentiation in the skin. Med Sci (Paris). 23: 34-36, 2007.
[CrossRef]
[PubMed]
Cheng WL, Lin TY, Tseng YH, Chu FH, Chueh PJ, Kuo YH, Wang SY. Inhibitory Effect of Human Breast Cancer Cell Proliferation via p21-Mediated G1 Cell Cycle Arrest by Araliadiol Isolated from Aralia cordata Thunb. Planta Med. 77: 164-168, 2011.
[CrossRef]
[PubMed]
Chimge NO, Makeyev AV, Waigel SJ, Enkhmandakh B, Bayarsaihan D. PI3K/Akt-dependent functions of TFII-I transcription factors in mouse embryonic stem cells. J Cell Biochem. 113: 1122-1131, 2012.
[CrossRef]
[PubMed]
Cho YS, Bae JM, Chun YS, Chung JH, Jeon YK, Kim IS, Kim MS, Park JW. HIF-1alpha controls keratinocyte proliferation by up-regulating p21(WAF1/Cip1). Biochim Biophys Acta. 1783: 323-333, 2008.
[CrossRef]
[PubMed]
Choi EJ. Hesperetin induced G1-phase cell cycle arrest in human breast cancer MCF-7 cells: involvement of CDK4 and p21. Nutr Cancer. 59: 115-119, 2007.
[CrossRef]
[PubMed]
Ciraolo E, Morello F, Hirsch E. Present and future of PI3K pathway inhibition in cancer: perspectives and limitations. Curr Med Chem. 18: 2674-2685, 2011.
[CrossRef]
[PubMed]
Dvory-Sobol H, Cohen-Noyman E, Kazanov D, Figer A, Birkenfeld S, Madar-Shapiro L, Benamouzig R, Arber N. Celecoxib leads to G2/M arrest by induction of p21 and down-regulation of cyclin B1 expression in a p53-independent manner. Eur J Cancer. 42: 422-426, 2006.
[CrossRef]
[PubMed]
Enshell-Seijffers D, Lindon C, Kashiwagi M, Morgan BA. Beta-catenin activity in the dermal papilla regulates morphogenesis and regeneration of hair. Dev Cell. 18: 633-642, 2010.
[CrossRef]
[PubMed]
Fang Y, Yu S, Braley-Mullen H. TGF-beta promotes proliferation of thyroid epithelial cells in IFN-gamma(-/-) mice by down-regulation of p21 and p27 via AKT pathway. Am J Pathol. 180: 650-660, 2012.
[CrossRef]
[PubMed]
Gottardi CJ, Gumbiner BM. Distinct molecular forms of beta-catenin are targeted to adhesive or transcriptional complexes. J Cell Biol. 167: 339-349, 2004.
[CrossRef]
[PubMed]
Guo X, Li W, Wang Q, Yang HS. AKT Activation by Pdcd4 Knockdown Up-Regulates Cyclin D1 Expression and Promotes Cell Proliferation. Genes Cancer. 2: 818-828, 2011.
[CrossRef]
Hirsch C, Campano LM, Wohrle S, Hecht A. Canonical Wnt signaling transiently stimulates proliferation and enhances neurogenesis in neonatal neural progenitor cultures. Exp Cell Res. 313: 572-587, 2007.
[CrossRef]
[PubMed]
Hoi CS, Lee SE, Lu SY, McDermitt DJ, Osorio KM, Piskun CM, Peters RM, Paus R, Tumbar T. Runx1 directly promotes proliferation of hair follicle stem cells and epithelial tumor formation in mouse skin. Mol Cell Biol. 30: 2518-2536, 2010.
[CrossRef]
[PubMed]
Huelsken J, Vogel R, Erdmann B, Cotsarelis G, Birchmeier W. beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin. Cell. 105: 533-545, 2001.
[CrossRef]
Ito M, Yang Z, Andl T, Cui C, Kim N, Millar SE, Cotsarelis G. Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding. Nature. 447: 316-320, 2007.
[CrossRef]
[PubMed]
Kamei J, Toyofuku T, Hori M. Negative regulation of p21 by beta-catenin/TCF signaling: a novel mechanism by which cell adhesion molecules regulate cell proliferation. Biochem Biophys Res Comm. 312: 380-387, 2003.
[CrossRef]
[PubMed]
Kim JS, Kim BS, Kim J, Park CS, Chung IY. The phosphoinositide-3-kinase/Akt pathway mediates the transient increase in Nanog expression during differentiation of F9 cells. Arch Pharm Res. 33: 1117-1125, 2010.
[CrossRef]
[PubMed]
Kishimoto J, Burgeson RE, Morgan BA. Wnt signaling maintains the hair-inducing activity of the dermal papilla. Genes Dev. 14: 1181-1185, 2000.
[PubMed]
Kobayashi K, Rochat A, Barrandon Y. Segregation of keratinocyte colony-forming cells in the bulge of the rat vibrissa. Proc Natl Acad Sci USA. 90: 7391-7395, 1993.
[CrossRef]
Le Belle JE, Orozco NM, Paucar AA, Saxe JP, Mottahedeh J, Pyle AD, Wu H, Kornblum HI. Proliferative neural stem cells have high endogenous ROS levels that regulate self-renewal and neurogenesis in a PI3K/Akt-dependant manner. Cell Stem Cell. 8: 59-71, 2011.
[CrossRef]
[PubMed]
Lee G, Goretsky T, Managlia E, Dirisina R, Singh AP, Brown JB, May R, Yang GY, Ragheb JW, Evers BM, Weber CR, Turner JR et al. Phosphoinositide 3-kinase signaling mediates beta-catenin activation in intestinal epithelial stem and progenitor cells in colitis. Gastroenterology. 139: 869-881, 2010.
[CrossRef]
[PubMed]
Liu C, Li Y, Semenov M, Han C, Baeg GH, Tan Y, Zhang Z, Lin X, He X. Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell. 108: 837-847, 2002.
[CrossRef]
Lo Celso C, Prowse DM, Watt FM. Transient activation of beta-catenin signalling in adult mouse epidermis is sufficient to induce new hair follicles but continuous activation is required to maintain hair follicle tumours. Development. 131: 1787-1799, 2004.
[CrossRef]
[PubMed]
MacDonald BT, Tamai K, He X. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell. 17: 9-26, 2009.
[CrossRef]
[PubMed]
Malanchi I, Peinado H, Kassen D, Hussenet T, Metzger D, Chambon P, Huber M, Hohl D, Cano A, Birchmeier W, Huelsken J. Cutaneous cancer stem cell maintenance is dependent on beta-catenin signalling. Nature. 452: 650-653, 2008.
[CrossRef]
[PubMed]
Masckauchan TN, Shawber CJ, Funahashi Y, Li CM, Kitajewski J. Wnt/beta-catenin signaling induces proliferation, survival and interleukin-8 in human endothelial cells. Angiogenesis. 8: 43-51, 2005.
[CrossRef]
[PubMed]
Oshima H, Rochat A, Kedzia C, Kobayashi K, Barrandon Y. Morphogenesis and renewal of hair follicle from adult multipotene stem cells. Cell. 104: 233-245, 2001.
[CrossRef]
Parrales A, Lopez E, Lopez-Colome AM. Thrombin activation of PI3K/PDK1/Akt signaling promotes cyclin D1 upregulation and RPE cell proliferation. Biochim Biophys Acta. 1813: 1758-1766, 2011.
[CrossRef]
[PubMed]
Perez-Moreno M, Jamora C, Fuchs E. Sticky business: orchestrating cellular signals at adherens junctions. Cell. 112: 535-548, 2003.
[CrossRef]
Perry JM, He XC, Sugimura R, Grindley JC, Haug JS, Ding S, Li L. Cooperation between both Wnt/{beta}-catenin and PTEN/PI3K/Akt signaling promotes primitive hematopoietic stem cell self-renewal and expansion. Genes Dev. 25: 1928-1942, 2011.
[CrossRef]
Reya T, Clevers H. Wnt signalling in stem cells and cancer. Nature. 434: 843-850, 2005.
[CrossRef]
[PubMed]
Rulifson IC, Karnik SK, Heiser PW, ten Berge D, Chen H, Gu X, Taketo MM, Nusse R, Hebrok M, Kim SK. Wnt signaling regulates pancreatic beta cell proliferation. Proc Natl Acad Sci USA. 104: 6247-6252, 2007.
[CrossRef]
[PubMed]
Saito T, Oda Y, Yamamoto H, Kawaguchi K, Tanaka K, Matsuda S, Iwamoto Y, Tsuneyoshi M. Nuclear beta-catenin correlates with cyclin D1 expression in spindle and pleomorphic sarcomas but not in synovial sarcoma. Hum Pathol. 37: 689-697, 2006.
[CrossRef]
[PubMed]
Sick S, Reinker S, Timmer J, Schlake T. WNT and DKK determine hair follicle spacing through a reaction-diffusion mechanism. Science. 314: 1447-1450, 2006.
[CrossRef]
[PubMed]
Suzuki K, Yamaguchi Y, Villacorte M, Mihara K, Akiyama M, Shimizu H, Taketo MM, Nakagata N, Tsukiyama T, Yamaguchi TP, Birchmeier W, Kato S et al. Embryonic hair follicle fate change by augmented beta-catenin through Shh and Bmp signaling. Development. 136: 367-372, 2009.
[CrossRef]
[PubMed]
Taylor G, Lehrer MS, Jensen PJ, Sun TT, Lavker RM. Involvement of follicular stem cells in forming not only the follicle but also the epidermis. Cell. 102: 451-461, 2000.
[CrossRef]
Vlad A, Rohrs S, Klein-Hitpass L, Muller O. The first five years of the Wnt targetome. Cell Signal. 20: 795-802, 2008.
[CrossRef]
[PubMed]
Xia J, Urabe K, Moroi Y, Koga T, Duan H, Li Y, Furue M. beta-Catenin mutation and its nuclear localization are confirmed to be frequent causes of Wnt signaling pathway activation in pilomatricomas. J Dermatol Sci. 41: 67-75, 2006.
[CrossRef]
[PubMed]
Yoshida M, Matsui Y, Iizuka A, Ikarashi Y. G2-phase arrest through p21(WAF1/Cip1) induction and cdc2 repression by gnidimacrin in human hepatoma HLE cells. Anticancer Res. 29: 1349-1354, 2009.
[PubMed]
Zhang Y, Xiang M, Wang Y, Yan J, Zeng Y, Yu J, Yang T. Bulge cells of human hair follicles: segregation, cultivation and properties. Colloids Surf B Biointerfaces. 47: 50-56, 2006.
[CrossRef]
[PubMed]
Zhang Y, Andl T, Yang SH, Teta M, Liu F, Seykora JT, Tobias JW, Piccolo S, Schmidt-Ullrich R, Nagy A, Taketo MM, Dlugosz AA, Millar SE. Activation of beta-catenin signaling programs embryonic epidermis to hair follicle fate. Development. 135: 2161-2172, 2008.
[CrossRef]
[PubMed]
Zhou BP, Deng J, Xia W, Xu J, Li YM, Gunduz M, Hung MC. Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control of epithelial-mesenchymal transition, Nature Cell Biol. 6: 931-940, 2004.
[CrossRef]
[PubMed]
|
CITED
0
|
